Short pulse laser machining of polymers enhanced with light absorbers for fabricating medical devices

ABSTRACT

A method of laser machining a polymer construct to form a stent that includes a bioresorbable polymer and an absorber that increases absorption of laser energy during laser machining. The laser cuts the tubing at least in part by a multiphoton absorption mechanism and the polymer and absorber have a very low absorbance or are transparent to light at the laser wavelength.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to laser machining tubing to form stents.

2. Description of the State of the Art

This invention relates to laser machining of devices such as stents.Laser machining refers to removal of material accomplished through laserand target material interactions. Generally speaking, these processesinclude laser drilling, laser cutting, and laser grooving, marking orscribing. Laser machining processes transport photon energy into atarget material in the form of thermal energy, photochemical energy, orboth. Material is removed by melting and blow away, directvaporization/ablation, or by formation of a plasma with ablation.

When a substrate is laser machined energy is transferred into thesubstrate. As a result, a region beyond the cutting edge is modified bythe energy, which affects the properties in this region. This region maybe referred to as the “laser affected zone” (LAZ). In general, thechanges in properties in this region are adverse to the properfunctioning of a device that is being manufactured. Therefore, it isgenerally desirable to reduce or eliminate energy transfer beyondremoved material, thus reducing or eliminating the extent ofmodification and size of the region affected.

One of the many medical applications for laser machining includesfabrication of radially expandable endoprostheses, which are adapted tobe implanted in a bodily lumen. An “endoprosthesis” corresponds to anartificial device that is placed inside the body. A “lumen” refers to acavity of a tubular organ such as a blood vessel.

A stent is an example of such an endoprosthesis. Stents are generallycylindrically shaped devices, which function to hold open and sometimesexpand a segment of a blood vessel or other anatomical lumen such asurinary tracts and bile ducts. Stents are often used in the treatment ofatherosclerotic stenosis in blood vessels. “Stenosis” refers to anarrowing or constriction of the diameter of a bodily passage ororifice. In such treatments, stents reinforce body vessels and preventrestenosis following angioplasty in the vascular system. “Restenosis”refers to the reoccurrence of stenosis in a blood vessel or heart valveafter it has been treated (as by balloon angioplasty, stenting, orvalvuloplasty) with apparent success.

The treatment of a diseased site or lesion with a stent involves bothdelivery and deployment of the stent. “Delivery” refers to introducingand transporting the stent through a bodily lumen to a region, such as alesion, in a vessel that requires treatment. “Deployment” corresponds tothe expanding of the stent within the lumen at the treatment region.Delivery and deployment of a stent are accomplished by positioning thestent about one end of a catheter, inserting the end of the catheterthrough the skin into a bodily lumen, advancing the catheter in thebodily lumen to a desired treatment location, expanding the stent at thetreatment location, and removing the catheter from the lumen.

In the case of a balloon expandable stent, the stent is mounted about aballoon disposed on the catheter. Mounting the stent typically involvescompressing or crimping the stent onto the balloon. The stent is thenexpanded by inflating the balloon. The balloon may then be deflated andthe catheter withdrawn. In the case of a self-expanding stent, the stentmay be secured to the catheter via a retractable sheath or a sock. Whenthe stent is in a desired bodily location, the sheath may be withdrawnwhich allows the stent to self-expand.

The structure of a stent is typically composed of scaffolding thatincludes a pattern or network of interconnecting structural elementsoften referred to in the art as struts or bar arms. The scaffolding canbe formed from wires, tubes, or sheets of material rolled into acylindrical shape. The scaffolding is designed so that the stent can beradially compressed (to allow crimping) and radially expanded (to allowdeployment).

Stents have been made of many materials such as metals and polymers,including biodegradable polymeric materials. Biodegradable stents aredesirable in many treatment applications in which the presence of astent in a body may be necessary for a limited period of time until itsintended function of, for example, achieving and maintaining vascularpatency and/or drug delivery is accomplished. Due to their temporarynature, biodegradable stents are often referred to as scaffolds.

Stents can be fabricated by forming patterns on tubes or sheets usinglaser machining. Even though the basic laser-material interaction issimilar, there are certain aspects that differ among types of materials(such as metals, plastics, glasses, and ceramics), i.e. differentabsorption characteristics. The properties of biodegradable polymerstend to be very sensitive to energy transfer from laser machining,depending on the laser wavelength and power. It is critical when forminga biodegradable polymer stent from a biodegradable construct using lasermachining that damage to the polymer material of the stent pattern fromthe laser energy is minimized. This requires judicious selection oflaser parameters that allow cutting of the polymer in a fast efficientmanner while minimizing damage to the polymer.

It has been found that selecting a combination of parameters such aspulse energy, wavelength, and laser pulse duration is critical indefined the optimal process conditions for the type of material. Shortpulse lasers can operate in a regime where absorption of energy by thepolymer is via a multi-photon process which generates a plasma plume. Anadvantage of this process is formation of a small or thin LAZ. However,even with the optimal parameters the cutting process can be slower thandesired with certain constructs, for example, constructs with thickwalls that are used for making peripheral scaffolds. In such situations,modifying the laser parameters to increase cutting speed can result inundesirable damage to the construct material which can adversely affectscaffold performance. In some situations, multiple passes of the laserover the polymer are required to cut completely through leading to longprocessing times. Therefore, methods are needed for increasing lasermachining speed without adversely affecting the material of asfabricated scaffolds.

SUMMARY OF THE INVENTION

Embodiments of the present invention include a method of laser machininga substrate to form a stent, comprising: providing a tube comprising apolymer and an absorber; and laser machining the polymer tube with alaser beam to form a scaffold, wherein the laser beam has a pulse widththat provides multiphoton absorption of laser energy from the laserbeam, wherein the laser beam has a wavelength such that the extinctioncoefficient of the polymer at the laser beam wavelength is less than 5%of the extinction coefficient of the polymer at one half the laser beamwavelength, wherein the absorber has a maximum absorbance at awavelength within 50 nm of one half the laser beam wavelength, andwherein the absorber increases absorption of the laser energy in thetube which allows the laser beam to cut through the wall in one pass ofthe laser beam using laser cutting speed of 4 to 20 in/min to form thescaffold.

Embodiments of the present invention include a method of laser machininga substrate to form a stent, comprising: providing a tube comprising apoly(L-lactide) (PLLA) and an absorber; and laser machining the polymertube with a laser beam having a pulse width of 1 to 12 ps and with alaser wavelength of 515 or 532 nm, wherein the absorber has a maximumabsorbance in a range between 200 and 300 nm and an extinctioncoefficient at least 2 times larger than the polymer in the range, andwherein the absorber increases absorption of the laser energy whichallows the laser machining to cut through the wall in one pass of thelaser beam using a laser cutting speed of 4 to 20 in/min to form ascaffold comprising structural elements.

Embodiments of the present invention include a method of laser machininga substrate to form a stent, comprising: providing a tube comprising abioresorbable aliphatic polyester polymer and an absorber; and lasermachining the polymer tube with a laser beam to form a scaffold, whereinthe laser beam has a pulse width that provides multiphoton absorption oflaser energy from the laser beam, wherein the polymer is transparent tolaser energy at a wavelength of the laser beam, and wherein the absorberhas a weight percent extinction coefficient at least 100 times greaterthan the polymer at one half the wavelength of the laser beam, andwherein the absorber increases ablation of the polymer by the laserbeam.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a stent.

FIG. 2 depicts a machine-controlled system for laser machining a tube.

FIG. 3 depicts a close-up axial view of a region where a laser beaminteracts with a tube.

FIG. 4 depicts the absorbance as a function of wavelength of the laserfor samples of polymers and absorbers.

DETAILED DESCRIPTION OF THE INVENTION

Embodiments of the present invention relate to methods of lasermachining of polymer constructs to manufacture thick-walled scaffoldssuch as those for use in peripheral vessels. More specifically, theseembodiments relate to increasing the speed of the laser machining oftubing in the fabrications of thick-walled scaffolds. The increase isaccomplished by including absorbers in the construct material thatincrease laser energy absorption in the tubing material withoutadversely affecting the mechanical, biocompatibility, or absorptionproperties of the polymer material of the scaffold. The increase inlaser energy absorption can be achieved without modifying any laserparameter or any combination of laser parameters such as pulse durationor width, wavelength, or pulse energy.

In general, stents can have virtually any structural pattern that iscompatible with a bodily lumen in which it is implanted. Typically, astent is composed a scaffold including a pattern or network ofcircumferential rings and longitudinally extending interconnectingstructural elements of struts or bar arms. In general, the struts arearranged in patterns, which are designed to contact the lumen walls of avessel and to maintain vascular patency.

An exemplary structure of a stent is shown in FIG. 1. FIG. 1 depicts astent 10 which is made up of struts 12 with gaps between the struts.Stent 10 has interconnected cylindrical rings 14 connected by linkingstruts or links 16. The embodiments disclosed herein are not limited tofabricating stents or to the stent pattern illustrated in FIG. 1. Theembodiments are easily applicable to other stent patterns and otherdevices. The variations in the structure of patterns are virtuallyunlimited.

A key step in the fabrication of a bioresorbable vascular scaffold islaser machining of the tubing to form the scaffold pattern. A scaffoldcan be fabricated by laser machining a construct or substrate such as atube to form the scaffold. Material is removed from selected regions ofthe construct which results in formation of the structure of the device.In particular, a stent may be fabricated by machining a thin-walledtubular member with a laser. Selected regions of the tubing may beremoved by laser machining to obtain a stent with a desired pattern ofstructural element or struts. Specifically, a laser beam can be scannedover the surface of tubing or the tubing can be translated and rotatedunder the beam resulting in removal of a trench or kerf extending allthe way through a wall of the tubing. When a starting and ending pointof a kerf meet, the region surrounded by the kerf drops out or isremoved by an assisting gas which creates a gap in the tube wall.

FIG. 2 depicts an embodiment of a portion of a machine-controlled systemfor laser machining a tube. Prior to laser machining, the wall of thetube can be free of any holes or gaps. In FIG. 2, a tube 200 is disposedin a rotatable collet fixture 204 of a machine-controlled apparatus 208for positioning tube 200 relative to a laser 212. According tomachine-encoded instructions, tube 200 is rotated and moved axiallyrelative to laser 212 which is also machine-controlled. The laserselectively removes the material from the tubing resulting in a patterncut into the tube. The tube is therefore cut into the discrete patternof the finished stent.

FIG. 3 depicts a close-up view of a laser beam 408 interacting with atube 414. Laser beam 408 is focused by a focusing lens 338 on tube 414.Tube 414 is supported by a controlled rotary collet 337 at one end andan optional tube support pin 339 at another end. A coaxial gas jetassembly 340 directs a cold gas jet or stream 342 that exits through anozzle 344 that cools the machined surface as the beam cuts and removesablated or ionized material. The gas stream also helps to remove debrisfrom the kerf and cool the region near the beam. Gas inlet is shown byan arrow 354. Coaxial gas jet nozzle 344 is centered around a focusedbeam 352. In some embodiments, the pressure of the supplied cooling gasis between 30 and 150 psi. An exemplary flow rate of the cooling gas isbetween 2 and 100 scfh, or more narrowly, 2 to 20 scfh, 20 to 50 scfh,50 to 70 scfh, or 70 to 100 scfh. Exemplary cooling gases or processgases include helium, hydrogen, argon, nitrogen, neon, oxygen, or amixture of those gases.

Biodegradable or bioresorbable polymers that may be suitable for stentscaffold applications include semi-crystalline polymers. In particular,these include polymers with a glass transition temperature (Tg) abovehuman body temperature, which is about 37° C. The polymer substrate orscaffold can be made in whole or in part from a single or a combinationof biodegradable polymers including, but not limited to, poly(L-lactide)(PLLA), polymandelide (PM), poly(caprolactone),poly(L-lactide-co-caprolactone), poly(D,L-lactide) (PDLLA),poly(D,L-lactide-co-caprolactone), polyglycolide (PGA),poly(glycolide-co-caprolactone), poly(L-lactide-co-glycolide) (PLGA),and poly(D,L-lactide-co-glycolide) (PDLGA). PLGA or PDLGA may includecopolymers containing different molar ratios of units derived fromL-lactide or D,L-lactide and glycolide, such as, 90:10, 75:25, 50:50,25:75, 10:90, or any composition in between.

Several properties of a scaffold are essential for performing itsfunction including, high radial strength to provide mechanical supportto a vessel and resistance to fracture. Fracture of a scaffold can occurduring crimping, during deployment, and after deployment in a vessel.Fracture can lead to a loss of radial strength, increase acutethrombogenicity, create vessel trauma, generate an embolic hazard and/orpotentially cause premature catastrophic failure of the scaffold. Priorto laser machining, the tube may be subjected to processing whichenhances radial strength and fracture resistance. Therefore, it isessential that the mechanical properties of the tube material bemaintained throughout the laser machining process. Localized energydeposition to the tube material during laser cutting can result inmodification of the desired microstructural properties or damage tolocalized regions.

Laser beam machining is one of most advanced non-contact type machiningtechnology used in micro and nano-fabrication to fulfill the need inhandling advanced engineering materials, stringent design requirements,intricate shape and unusual size. Laser machining methods which employshort pulse widths in a range of a picosecond (=10¹²) (“Picosecond”lasers) and in the range of a femtosecond (=10⁻¹⁵) have been found to bepromising in minimizing damage in the laser processing of bioabsorbablepolymer scaffolds. “Pulse width” or “pulse duration” refers to theduration of an optical pulse versus time. The duration can be defined inmore than one way. Specifically, the pulse duration can be defined asthe full width at half maximum (FWHM) of the optical power versus time.Picosecond and femtosecond lasers offer unique advantages for theremoval of precise amount of materials with minimum thermal or UV damageto the surrounding material. In general, the picosecond lasers havepulse widths between about 1 and 15 ps, 1 and 12 ps, or 1 and 20 ps andthe femtosecond lasers have pulse widths between 10 and 800 fs.

The two fundamental mechanisms involved in the laser ablation arebelieved to be photothermal and photochemical. In the photothermalmechanism the material is ablated by melting and vaporizing, whereas inthe photochemical mechanism the photo energy of light is used to breakthe chemical bonds of the polymer directly. The chemical bonds betweenatoms and molecules of the substrate are broken resulting in formationof gaseous species which are removed from the substrate.

Laser ablation of material from a substrate can occur by a thermalmechanism, a nonthermal mechanism, or a combination of both.Longer-pulse lasers, for example, remove material from a surfaceprincipally through a thermal mechanism. In a thermal mechanism, thelaser energy that is absorbed results in a temperature increase at andnear the absorption site and material is removed by conventional meltingor vaporization. Thermal damage of uncut substrate material can occurdue to melting and thermal diffusion into a region or zone of materialat the machining edge.

Lasers with femtosecond pulse duration are of particular interest forablating material as the pulse duration is less than the typicalthermalization characteristic time (i.e., time to achieve thermalequilibrium) which is a few picoseconds. Due to a much smaller thermaldiffusion depth, femtosecond laser machining may be considered to removematerial by a completely or nearly completely nonthermal mechanism. Apicosecond laser removes material mostly through a nonthermal mechanism,but also with some degree of thermal mechanism for some materials thatis enough to cause some thermal damage to a substrate.

More specifically, the nonthermal mechanism involves optical breakdownin the target material which results in material removal. During opticalbreakdown of material, a very high free electron density, i.e., plasma,is produced through mechanisms such as multiphoton absorption andavalanche ionization. With optical breakdown, the target material isconverted from its initial solid-state directly into fully ionizedplasma on a time scale too short for thermal equilibrium to beestablished with a target material lattice. Therefore, there isnegligible heat conduction beyond the region removed.

As described in U.S. Patent Publication Number 20110307050, it has beenfound that the nonthermal mechanism can also cause damage to the uncutmaterial which arises from photochemical affects that result in voidswithin the uncut material. However, it has also been recognized that thedamage caused by the thermal and nonthermal mechanisms can be reduced orminimized by laser machining at a laser wavelength such that the polymerhas an absorption coefficient at the laser wavelength that issubstantially less than the maximum absorbance of the polymer.

In the laser machining of the present invention, the polymer of a lasermachined construct has a very low or no absorbance at the wavelength ofthe laser and thus is almost or completely transparent to the laserbeam. Energy is absorbed by the construct via a nonthermal mechanism dueto the short pulse duration of the laser.

In some embodiments, the absorbance, extinction coefficient, orextinction coefficient based on weight percent of the polymer at thelaser wavelength can be less than 1%, less than 5%, less than 10%, lessthan 20%, 0.1 to 1%, 1% to 5%, 5 to 10%, 10 to 20%, 20 to 40%, or 40 to60% of the absorbance, extinction coefficient, or extinction coefficientof the polymer at one half the laser wavelength based on weight percentof the polymer. Additionally or alternatively, the laser wavelength maybe 100 nm, 200 nm, 300 nm, 400 nm, 100 to 200 nm, 200 to 300 nm, 300 to400 nm more than the wavelength of maximum absorbance of the polymer.

The extinction coefficient is a measure of how strongly a substanceabsorbs light at a particular wavelength. For a well-defined, puremolecular species in, for example, a solvent it is usually representedby units of AU-L/mole-cm where:

AU=absorbance unitL=litercm=centimeter (path length)In the case of a polydisperse material, such as a polymer, theextinction coefficient can be defined in terms of weight percent andhave the units of AU/wt %-cm. The extinction coefficient is a functionof wavelength.

For example, PLLA can be machined with a short pulse laser at 515 nmwavelength even though PLLA does not absorb appreciably at 515 nmwavelength. In general, bioresorbable polyester polymers are completelytransparent to visible wavelengths from 400-800 nm. In a nonthermalmechanism, absorption of the laser light is accomplished via anon-linear optical process that occurs due to the very high intensity ofthe short pulse laser. In PLLA, the most accessible chromophore is theester bond, where a “chromophore” refers to a chemical group capable ofselective light absorption resulting in the coloration of certainorganic compounds. Instead of a single photon being adsorbed,multi-photon adsorption process occurs. Essentially, two 515 nm photonsare adsorbed. The energy of two, 515 nm photons is equivalent to asingle 258 nm photon and the ester bond in PLLA does absorb minimally atthis wavelength.

As described in U.S. Patent Publication Number 20110307050, short pulselaser process parameters can be adjusted and defined for particularpolymers to provide a balance between thermal and nonthermal damage thatadversely affects mechanical properties of a finished scaffold, such asradial strength, elongation at break, or fracture resistance. The laserparameters that are adjusted include the pulse width, pulse repetitionrate, power, and wavelength of the laser energy.

In particular, the extent and depth of the damage caused by thephotochemical mechanism can be controlled by laser parameters such aspulse width and wavelength. It is believed that in laser machiningpolymers, there is a tradeoff between damage caused by a thermal andnonthermal mechanism. Although the character of the damage caused byeach mechanism is different, both can adversely affect scaffoldperformance. The laser parameters (e.g., pulse width and wavelength) canbe adjusted to reduce the photochemical effects, but with some increasein the thermal mechanism.

Specifically, with respect to wavelength adjustment, the lower thesingle-photon absorption coefficient of a polymer at a given range ofwavelength, the lower is the thermal effect on the polymer substrate.The photochemical removal increases and thermal side-wall damagedecreases as the wavelength changes from a wavelength range of lowsingle-photon absorption by the polymer to high single-photon absorptionby the polymer. Additionally high energy photons (in or near the UV)have the potential to photochemically damage polymer areas around thecut. With respect to pulse width, as the pulse width in the femtosecondor picosecond range decreases, the photochemical removal at a fixedpulse energy increases and the thermal sidewall damage decreases.Parameters can be adjusted by determining a combination of wavelengthand pulse width, for example, that minimize adverse photochemicaleffects such as voids and variation of mechanical properties near thecut sidewall surface as well as minimizing adverse thermal effects suchas melting.

For example, laser wavelength found to be advantageous for PLLA is inthe visible light spectrum from 390 to 800 nm. More narrowly, the laserwavelength is in the green spectrum or from about 496 to 570 nm, or evenmore narrowly 532 nm or 515 nm. The pulse width found be advantageouscan be 0.8 ps or less, 0.8-1 ps, 1-5 ps, 5-10 ps, 10-12 ps, 12-15 ps, or15 to 20 ps. A 10 ps laser with 532 nm wavelength at repetition rate of80 kHz results in minimal damage to the PLLA scaffold as compared toother combinations of wavelengths with lower pulse widths.

Minimizing photochemical damage may correspond to minimizing thethickness of a laser affected zone next to the laser machined edge thatincludes voids. For example, the thickness of the region can be lessthan 2 microns, less than 5 microns, less than 20 microns, or less than30 microns. The void region can be 1-2 microns, 2-5 microns, 2-10microns, 2-20 microns, or 5-10 microns.

Mechanical properties such as the modulus have been found to vary withdistance from a cut surface. Additionally or alternatively, minimizingphotochemical damage can help reduce the modulus variation of a cutstent with distance in the laser affected zone. The parameters may beadjusted to obtain faster convergence of the modulus toward a modulus ofan undamaged polymer substrate. The modulus may converge at less than 4microns, less than 8 microns, or less than 20 microns from the machinededge surface. The modulus may converge at between 1-4 microns, 4-8microns, or 8-20 microns from the machined edge surface. The modulus mayconverge at 4 microns or less, 8 microns or less, 15 microns or less, or20 microns or less from the machined edge surface.

The pulse width may be adjusted at a given wavelength to avoid excessivemelting, even with an appropriate level of cooling during machining.Excessive melting may correspond to greater than 0.25, 0.5, greater than1 micron, 0.25 to 0.5 micron, or 0.5 to 1 micron thickness of meltedmaterial.

Additional laser parameters are also selected to be used with desiredlaser wavelength and pulse duration described herein. As described inU.S. Patent Publication Number 20110307050, laser machining a tube tomake a coronary scaffold includes selecting the average laser power orpower (energy per pulse×repetition rate) and repetition rate for a givenpulse width and wavelength to provide a fluence (energy per pulse/spotsize of beam) that is high enough so that the beam cuts the substrateall the way through the polymer tubing. The beam spot size is generallyis 10 to 20 microns, but can be less than 10 or greater than 20 micronsdepending on the application. A pulse energy and fluence (based on a 10micron spot size) for laser cutting polymers can be 4 to 200 μJ and0.5-200 J/cm2, respectively. The average power per pulse of a beam canbe 0.5 to 4 W. More narrowly, the power can be 0.5 to 1 W, 1 to 1.5 W,1.5 to 1.8 W, 1.8 to 2 W, 2 to 2.2 W, 2.2 to 2.5 W, 2.5 to 2.8 W, 2.8 to3 W, 3 to 3.2 W, 3.2 to 3.5 W, 3.5 to 3.8 W, 3.8 to 4 W. For a 10 pspulse width laser, the repetition rate can be 25 to 100 kHz, 25 to 50kHz, 50 to 60 kHz, 60 to 80 kHz, or 80 to 100 kHz. Exemplary laserparameters for laser machining are additionally are given in Table 1.

Additionally, the repetition rate and cooling gas flow rate (e.g., inSCFH He) are adjusted or selected in combination to reduce or minimizethermal effects (e.g., melting at surface of cut) and to maximizecutting speed. The cutting speed is the scan rate of the laser beam overthe surface of a construct or substrate. Exemplary cutting speed is 4 to20 in/min, or more narrowly, 4 to 8, 8 to 12, or 12 to 20 in/min. Theseranges of cutting speed provide an acceptable process time for cutting acoronary or peripheral scaffold.

Bioabsorbable polymer scaffolds for coronary artery treatment can have alength between 8 to 38 m, or more narrowly, between 12 and 18 mm. Suchcoronary scaffolds may be laser cut from polymer tubes with a diameterbetween 2.5 mm to 4.5 mm and with a wall thickness of 100-250 microns ormore narrowly 100 to 160 microns or 160 to 250 microns. A bioabsorbablepolymer scaffold for peripheral treatment, for example, superficialfemoral artery (SFA) treatment is typically longer, has a largerdiameter, and has thicker struts than a coronary scaffold. For example,the scaffolds may have a length 18 and 38 mm, 38 and 60 mm or evenbetween 60 and 200 mm. An SFA scaffold may be cut from tubing with adiameter of between 5-10 mm, 6-8 mm and a wall thickness of greater than160 microns, for example, 160 to 250 microns, 180 to 250 microns, 250 to300 microns, 300 to 350 microns, 350 to 400 microns, or greater than 400microns.

As described herein, a construct such as a tube can have walls that aretoo thick for the laser beam with a cutting speed within these rangesand that also has a desired set of parameters including wavelength,pulse width, and laser power to cut all the way through the wall in onepass. The desired set of parameters may be those described herein thatreduce or minimized both nonthermal and thermal effects.

In general, the repetition rate and cutting speed are directlyproportional, i.e., the faster the repetition rate, the faster thecutting speed, resulting in a lower process time per scaffold. However,as the repetition rate is increased, the thermal effects tend toincrease. Thus, the repetition rate may be limited to the rangesdisclosed herein in order to keep the thermal effects acceptable.

An increase in the cooling gas flow rate can mitigate the thermaleffects from the increased repetition rate, allowing a higher repetitionrate, and thus cutting speed. However, the increase in the cooling ratemay be insufficient to limit thermal effects.

TABLE 1 Exemplary Laser parameters Parameter Value Wavelength, nm 532 nmor 515 nm Polarization Circular Average laser power, W 1.5-3.0 Pulseenergy 21 μJ Pulse width 12 ps Repetition rate 80 kHz 100 kHz Gas(Helium) Flowrate, SCFH 6 to 10 Nozzle to substrate distance 0.9 mm Beamsize 8 mm cutting speed, inch/min 4 to 16

Due to the larger strut thickness, as well as the overall longer lengthsof scaffolds, the process times for laser machining a SFA scaffold canbe much longer than for a coronary scaffold. Table 2 lists theapproximate times to laser cut a coronary scaffold and SFA scaffolds,each made of PLLA.

TABLE 2 Laser Machining Times for Resorbable Coronary and SFA Scaffoldsper Pico Laser Head Bioresorbable Scaffold Laser Machining Time(minutes) 3.0 × 18 mm (coronary) 2.3 6.0 × 60 mm (SFA) 40 6.0 × 120 mm(SFA) 80 (estimated)

The laser parameters for both types of scaffolds are the same and arebased on those derived for the coronary scaffold as described above:wavelength of 515 nm and pulse duration of 6 picoseconds. The strutwidth of the coronary scaffold is 158 microns and the strut width of theSFA scaffold is 300 microns.

Lasing times for the SFA scaffolds are up to 20 times longer than thosefor coronary. One reason for this is that that larger strut thickness ofthe SFA scaffold requires multiple passes (2-3) for the picosecond laserto cut through the PLLA tube. The pulse power is not high enough to cutall the way through the SFA tubing in one pass. A second reason is theoverall much larger size of the SFA scaffolds. The slow processing timeincreases the production cost.

The processing time for the SFA scaffold for the same pulse duration canbe increased by increasing the laser power, for example, to the pointthat the laser beams cut through in one pass so that multiple passeswould not be necessary. However, increasing power could result inincreased scaffold damage that would adversely affect scaffoldperformance.

Absorptivity of the bioresorbable polymer such as PLLA is limited by themulti-photon adsorption process which is not efficient. The inventorshave found a way to increase the absorption of laser energy of abioresorbable polymer (e.g., PLLA) at a specified laser wavelength(e.g., 515 nm) without increasing the power of the laser and causingincreased scaffold damage and which also allows single pass cutting andfaster movement of the PLLA tube under the laser.

Embodiments of the present invention include polymer constructs such astubing made from compositions composed of biocompatible, absorbingmaterial or absorbers and polymers such as polyester bioresorbablepolymers. The absorbers absorb laser energy during laser machining andincrease the amount of energy absorbed by composition from the laser.

Embodiments further include methods that provide for faster lasercutting with short pulse lasers that cut the polymer at least in part bya multi-photon absorption process. Such short pulse lasers may have apulse duration 80 fs to 20 ps, or more narrowly 80 to 100 fs, 100 to 500fs, 500 fs to 1 ps, 1 to 5 ps, 5 to 10 ps, 10 to 12 ps, or 12 to 20 ps.The absorber in the composition may increase energy absorptionsufficient to provide one pass cutting of the scaffold pattern such thatthe laser beam cuts all the way through the wall of a construct such asa tube in one pass at any of the disclosed laser parameter describedherein.

The embodiments are applicable to laser machining any type of polymerconstruct, such as a tubing of any thickness. However, the increasedenergy absorption provided by the absorber is particularly critical forlaser machining thicker-walled tubes used for fabricating SFA scaffolds.In particular, the polymer tubing can have a thickness greater than 160microns, greater than 180 microns, or greater than 200 microns. Thethickness can be 160 to 200 microns, 200 to 250 microns, 250 to 300microns, or greater than 300 microns.

A polymer construct, such as a tube, that includes an absorber asdescribed herein may allow one pass cutting using a laser with thedesired laser parameters. It is believed that the absorber increases theabsorption of laser energy by the construct which is used for ablation.Therefore, the energy deposited into the construct is used moreefficiently, i.e., more of the energy deposited is used for ablation. Incontrast, it is believed that manipulating laser parameters to increasethe amount of energy or energy per unit time deposited into theconstruct (i.e., wavelength, pulse width, power, repetition rate) mayallow higher cutting speed with one pass cutting, however, the energydeposited in not necessarily used more efficiently. It is believed thatthe increased energy is used for ablation, but also results in increaseddamaged to the uncut substrate.

The present invention is applicable to laser machining constructs toform scaffolds made from or including any type of polymer, inparticular, bioresorbable aliphatic polyesters. Exemplary polymers asidefrom PLLA include polyglycolide (PGA), poly(4-hydroxybutyrate) (P4HB),polycaprolactone (PCL), poly(trimethylene carbonate) (PTMC),poly(butylene succinate) (PBS), poly(p-dioxanone) (PDO), and copolymersthereof. The copolymers can be random, alternating, or block copolymers.Additional bioresorbable polymers include poly(D-lactide),poly(L-lactide-co-glycolide), poly(L-lactide-co-D,L-lactide),poly(glycolide-co-caprolactone), poly(D,L-lactide-co-caprolactone),poly(L-lactide-co-glycolide) (PLGA), and poly(D,L-lactide-co-glycolide)(PDLGA). The PLGA or PDLGA includes those having a mole % of (LA orDLA:GA) of 85:15 (or a range of 82:18 to 88:12), 95:5 (or a range of93:7 to 97:3), or commercially available PLGA or PDLGA productsidentified being 85:15 or 95:5 PLGA or PDLGA.

In general, the absorbers do not absorb appreciably at the wavelength,λ, of the short pulse laser. In some embodiments, the absorber has noabsorbance or is transparent at the wavelength, λ, of the short pulselaser. However, the absorber may have appreciable absorbance at λ/2.

In some embodiments, the absorber may have its maximum absorbance at awavelength within a range of λ/2±100 nm; within a range of λ/2±50 nm;within a range of λ/2±20 nm; within a range of λ/2±10 nm; within a rangeof λ/2±5 nm; or within a range of λ/2±1 nm, where “range of λ/2±100 nm,”for example, can refer to a range λ/2+100 nm, λ/2-100 nm, or both.

Alternatively or additionally, the absorber may have its maximumabsorbance at a wavelength within a range of λ/2±100 nm; within a rangeof λ/2±50 nm; within a range of λ/2±20 nm; within a range of λ/2±10 nm;within a range of λ/2±5 nm; or within a range of λ/2±1 nm of the maximumabsorbance of the polymer of the construct.

In some embodiments, the absorbers are completely transparent or have noabsorbance at the wavelength of the laser. Alternatively oradditionally, the extinction coefficient or weight percent extinctioncoefficient of the absorber may be at least 2, 5, 10, 20, 100, 1000,10,000, and 100,000 times larger at λ/2 than at λ. Alternatively oradditionally, the extinction coefficient or extinction coefficientweight percent of the absorber may be at least 2 to 5, 5 to 10, 10 to20, 20 to 100, 100 to 1000, 1000 to 10,000, or 10,000 to 100,000 largerat λ/2 than at λ.

Alternatively or additionally, the extinction coefficient or weightpercent extinction coefficient of the absorber may be at least 2, 5, 10,20, 100, 1000, 10,000, or 100,000 times larger at λ/2 than the polymerof the construct at λ/2. Alternatively or additionally, the extinctioncoefficient or weight percent extinction coefficient of the absorber maybe at least 2 to 5, 5 to 10, 10 to 20, 20 to 100, 100 to 1000, 1000 to10,000, or 10,000 to 100,000 larger at λ/2 than the polymer of theconstruct at λ/2.

In exemplary embodiments, the laser has a pulse with of 6 to 15 ps and awavelength of 515 nm. In these embodiments, absorbers useful for lasermachining aliphatic polyesters such as PLLA may have strong absorptionin the Ultraviolet (UV) range or in the range of 200 to 400 nm.Specifically, the absorber may have its maximum absorbance at awavelength (lambda max) and/or have at least some absorbance of laserlight within 100 nm, 50 nm, 20 nm, 10 nm, 5 nm, or 1 nm of λ/2 or 258nm. Alternatively or additionally, the absorber may have at least someabsorbance of laser light within 100, 50, 20, or 10 nm of λ/2 or 258 nm.Alternatively or additionally, the extinction coefficient of theabsorber may be at least 5, 10, or 20 times larger at λ/2 or 258 nm thanat λ.

The polymer tubing including the absorber can be formed by mixing theabsorber in powder or liquid form with the polymer in an extruder duringthe tube formation process. The absorber can be metered into the resinhopper on the extruder. The absorber should be temperature stable so itwill not degrade or deteriorate from the extrusion process necessary toform the polymer tube. For example, the extrusion temperature of PLLA isgreater than 173 deg C, greater than 200 deg C, 180 to 200 deg C, 180 to220 deg C. The absorber should also possess high biocompatibility sinceit will be released when the polymer bioresorbs in the body. Theabsorber may be dispersed uniformly throughout the polymer construct.

In some embodiments, the absorber has a melting point lower than theextrusion temperature. Thus, the absorber melts during extrusion and isdispersed throughout the polymer.

Additionally, it is desirable that the absorber content in the tubing orscaffold be low enough that the mechanical properties of the scaffoldare not adversely affected. Therefore, it is desirable that theabsorbance increase to the construct per unit weight of the absorber inthe construct be as high as possible. In some embodiments, the contentof the absorber in the tubing is less than 0.001 wt %, less than 0.01 wt%, less than 0.1 wt %, 0.001 to 1 wt %, 0.001 to 0.01 wt %, 0.01 to 0.1wt %, or 0.001 to 0.1 wt %. A polymer construct composed of a polymermay have an absorber content in any of the above disclosed ranges thatalso has any of the disclosed absorber properties or ranges disclosedherein. Absorbers that include a phenyl ring in their structure may beused with lasers with a wavelength in the green spectrum or from about496 to 570 nm, or even more narrowly 532 nm or 515 nm since the phenylring absorbs in the UV range. Exemplary absorbers with phenyl rings fora bioresorbable polymer that are strong absorbers in the UV rangeinclude butylated hydroxytoluene (BHT) and methyl paraben.

BHT, which is shown below, is an anti-oxidant free radical scavengercurrently present in everolimus to protect it from degradation. BHT iswidely used as an anti-oxidant in drugs and foodstuffs.

Methyl Paraben, shown below, is an antimicrobial and antifungal agentwhich occurs naturally in blueberries. Methyl paraben is used widely inparenteral drugs as a preservative. Consequently, it is a substance thatis currently administered directly into the bloodstream.

The effectiveness of BHT and methyl paraben as absorbers in PLLA forlaser machining with a laser with a wavelength of 515 nm was considered.UV-visible spectra was collected on four types of samples, two PLLAtubing samples, BHT, and methyl paraben. The tubing samples wereprepared from two different sources of PLLA. The PLLA tubing was made byextrusion and then was radial expanded to a larger diameter using blowmolding at a temperature above the Tg of PLLA.

One tubing sample was prepared from PLLA obtained from PURAC,Lincolnshire, Ill., Lot 10805N5, XLHRSA2075771-01. The other tubingsample was prepared from PLLA obtained from Evonik, Birmingham, Ala.,Lot 20228N5, XLHRSA2075771-03.

The UV-vis spectra was collected in dichloromethane (CH₂Cl₂) as it is agood solvent for these compounds, including PLLA, and has a UV cutoff ata low wavelength of 233 nm. The UV cutoff of a solvent is the wavelengthat which the solvent absorbance in a 1 cm path length cell is equal to 1AU (absorbance unit) using water in the reference cell. A solvent forstudying the absorbance of a substance should be both a good solvent forthe substance and have a UV cutoff below that of the substance since thesubstance in the solvent is not visible below that of the UV cutoff ofthe solvent.

FIG. 4 depicts the absorbance as a function of wavelength of the laserfor each sample. Table 3 includes the lambda max and weight percentextinction coefficients in CH₂Cl₂ at λ/2 or 258 nm for the four samples.Lambda Max is the wavelength of maximum absorption.

TABLE 3 Lambda Max and Weight Extinction Coefficients at 258 nm. WeightPercent Extinction Coefficient at 258 nm Substance Lambda Max (nm)(units AU/cm-wt %) PURAC PLLA 230-235 1.64 × 10⁻² Evonik PLLA 230-2351.56 × 10⁻² BHT 234, 281 (two peaks) 26.3 Methyl Paraben 250 991

Weight percent extinction coefficient is defined by the equation:A=ε_(%) b wt % where

A=absorbance in AU

ε%=weight percent extinction coefficient

b=optical path length (cm)

wt %=wt % of solute in solution or matrix.

The PLLA from both vendors has a low absorbance at λ/2 or 258 nm. Insome cases, differences in how the expanded PLLA tubing is laser cutwere observed. That is some lots of tubing cut easier than others, i.e.,at a given laser power, the laser cuts through the tube wall faster. Onemechanism for this may be a differing UV absorbance between lots of PLLAexpanded tubing. It is believed that different levels of stannousoctoate in the expanded tubing may change the resin UV absorbance, andconsequently, change the laser cutting. Stannous octoate is a yellowcompound which absorbs in the UV. Stannous octoate is a catalyst used inthe polymerization to synthesize PLLA from monomer. The tubes may,therefore, contain residual stannous octoate.

Compared to PLLA, both BHT and methyl paraben absorb much more stronglyin the UV. FIG. 4 shows the UV spectra overlaid for these foursubstances. BHT and especially methyl paraben are much strongerabsorbers at λ/2 or 258 nm than PLLA from either vendor. For the listedconcentrations in weight percent, at λ/2 or 258 nm, the absorbance ofPLLA is about 0.02 AU while the absorbance of methyl paraben is about1.1 AU and the absorbance of BHT is about 0.3 AU. The weak absorbance ofPLLA at λ/2 or 258 nm is due to the ester bond energy absorbance whichhas a maximum absorbance at a much shorter wavelength, 230-235 nm.

The high absorbance of BHT and methyl paraben at λ/2 or 258 nm shown inFIG. 4 indicates that only a small amount of BHT or methyl paraben isneeded to be added to the PLLA to greatly enhance the UV absorbance ofPLLA tubing. Table 3 lists the quantities of BHT or methyl paraben thatmay be added to PLLA to increase the UV absorbance two times and tentimes at λ/2 or 258 nm. It is expected that these small amounts of addedUV absorber will not alter the mechanical properties of the PLLA oraffect its degradation properties. BHT and methyl paraben are smallmolecules that will be released from the PLLA as it resorbs.

TABLE 3 Percent Weight Loading Needed to Increase PLLA UV AbsorbanceWeight Percent in PLLA Weight Percent in PLLA Needed to Double theNeeded to Increase the Substance 258 nm Absorbance 258 nm Absorbance 10XBHT 0.06 0.6 Methyl Paraben 0.0016 0.016

Additional absorbers that have strong UV absorbance, include a phenylring, and are biocompatible include sodium benzoate, benzoic acid,benzyl alcohol, phenoxyl alcohol, gentisic acid, butylated hydroxylanisole, ethyl benzoate, methyl gallate, ethyl gallate, propyl gallate,ethyl paraben, propyl paraben, benzyl benzoate, resveratrol, alphatocopherol.

All of these compounds have at least one phenyl ring which isresponsible for their strong UV absorbance. Additionally, all of thesecompounds have a history of use in intravenous or parenteral drugs, arefound naturally in the body, or are approved for use in foodstuffs. Thecompounds are at least as chemically stable as PLLA, with a few beingeven more thermally stable.

Additionally, inorganic or metal based substances may be used as the UVabsorbers. The metal ions of tin, iron, magnesium, and zinc arebiocompatible. Metallic or inorganic UV absorbers may include stannousoctoate, stannous fluoride, ferrous hydroxide, ferrous fumarate, ferrousgluconate, ferrous sulphate, magnesium carbonate, magnesium citrate,magnesium gluconate, magnesium oxide, magnesium hydroxide, magnesiumphosphate, magnesium salicylate, magnesium sulphate, magnesiumtrisilicate, zinc acetate, zinc carbonate, zinc gluconate, zinc oxide,zinc stearate, zinc sulphate, zinc sulphide, and zinc undecylenate.

In some embodiments, the construct is free of absorbers that absorbstrongly at the laser wavelength, for example, absorbers that have awavelength of maximum absorption within 20 nm, 30 nm, or 10 nm of thelaser wavelength are excluded. For example, visible dyes may beexcluded. In some embodiments, the absorbers are completely transparentat the laser wavelength.

For machining a PLLA substrate, the absorbers may include onlysubstances that absorb light at wavelengths less than 400 nm when usedwith short pulse lasers in the picosecond to femtosecond rangesdisclosed herein, and that emit light at wavelengths greater than 400nm.

In further embodiments, drugs or therapeutic agents that absorb stronglyin the UV range may be used as absorbers. Exemplary drugs that arestrong UV absorbers include salicylic acid, acetyl salicylic acid(aspirin), dexamethasone, dexamethasone acetate, momentasone, clobetasolfuroate, and prednisone.

Embodiments of the invention further include a tube or construct priorto laser machining that includes the polymer and the absorber at any ofthe contents described herein. The embodiments further include ascaffold after laser machining including the polymer and the absorber atany of the contents described herein. The scaffold can further have thedisclosed limited damage such as voids and variation in mechanicalproperties disclosed herein.

The following definitions apply herein:

All ranges include the endpoints and any value within the endpoints,unless otherwise specified.

Polymers can be biostable, bioabsorbable, biodegradable, bioresorbable,or bioerodable. Biostable refers to polymers that are not biodegradable.The terms biodegradable, bioabsorbable, bioresorbable, and bioerodable,as well as degraded, eroded, and absorbed, are used interchangeably andrefer to polymers that are capable of being completely eroded orabsorbed when exposed to bodily fluids such as blood and can begradually resorbed, absorbed, and/or eliminated by the body.

“Radial strength” of a stent is defined as the minimum pressure at whicha stent experiences irrecoverable deformation.

“Stress” refers to force per unit area, as in the force acting through asmall area within a plane. Stress can be divided into components, normaland parallel to the plane, called normal stress and shear stress,respectively. True stress denotes the stress where force and area aremeasured at the same time. Conventional stress, as applied to tensionand compression tests, is force divided by the original gauge length.

The “maximum load” or ultimate load is the absolute maximum load (force)that a structure can bear without failing.

“Strength” refers to the maximum stress along an axis which a materialwill withstand prior to fracture. The ultimate strength is calculatedfrom the maximum load applied during the test divided by the originalcross-sectional area.

“Modulus” may be defined as the ratio of a component of stress or forceper unit area applied to a material divided by the strain along an axisof applied force that results from the applied force. The modulus is theinitial slope of a stress-strain curve, and therefore, determined by thelinear Hookean region of the curve. For example, a material has both atensile and a compressive modulus.

“Strain” refers to the amount of elongation or compression that occursin a material at a given stress or load.

“Elongation” may be defined as the increase in length in a materialwhich occurs when subjected to stress. It is typically expressed as apercentage of the original length.

“Elongation to Break” is the strain on a sample when it breaks. It isusually is expressed as a percent.

The “glass transition temperature,” Tg, is the temperature at which theamorphous domains of a polymer change from a brittle, glassy vitreousstate to a solid deformable, rubbery or ductile state at atmosphericpressure. In other words, the Tg corresponds to the temperature wherethe onset of segmental motion in the chains of the polymer occurs. Tg ofa given polymer can be dependent on the heating rate and can beinfluenced by the thermal history of the polymer. Furthermore, thechemical structure of the polymer heavily influences the glasstransition by affecting mobility.

While particular embodiments of the present invention have been shownand described, it will be obvious to those skilled in the art thatchanges and modifications can be made without departing from thisinvention in its broader aspects. Therefore, the appended claims are toencompass within their scope all such changes and modifications as fallwithin the true spirit and scope of this invention.

What is claimed is:
 1. A method of laser machining a substrate to form astent, comprising: providing a tube comprising a polymer and anabsorber; and laser machining the polymer tube with a laser beam to forma scaffold, wherein the laser beam has a pulse width that providesmultiphoton absorption of laser energy from the laser beam, wherein thelaser beam has a wavelength such that the extinction coefficient of thepolymer at the laser beam wavelength is less than 5% of the extinctioncoefficient of the polymer at one half the laser beam wavelength,wherein the absorber has a maximum absorbance at a wavelength within 50nm of one half the laser beam wavelength, and wherein the absorberincreases absorption of the laser energy in the tube which allows thelaser beam to cut through the wall in one pass of the laser beam usinglaser cutting speed of 4 to 20 in/min to form the scaffold.
 2. Themethod of claim 1, wherein the absorber is transparent to the laser beamat the wavelength of the laser beam.
 3. The method of claim 1, whereinthe polymer is an aliphatic polyester polymer.
 4. The method of claim 1,wherein a wall of the tube has a thickness of greater than 180 microns5. The method of claim 1, wherein a wall of the tube has a thickness of100 to 160 microns.
 6. The method of claim 1, wherein an extinctioncoefficient or weight percent extinction coefficient of the absorber isat least 5 times larger at one half the laser beam wavelength than atthe laser beam wavelength.
 7. The method of claim 1, wherein anextinction coefficient or weight percent extinction coefficient of theabsorber is at least 5 times larger at one half the laser beamwavelength than the polymer at one half the laser beam wavelength. 8.The method of claim 1, wherein an extinction coefficient of the absorberis at least 5 times larger at one half the laser beam wavelength than atthan at the laser beam wavelength.
 9. The method of claim 1, wherein acontent of the absorber in the tube is 0.001 to 0.1 wt %.
 10. The methodof claim 1, wherein the pulse width is 80 fs to 20 ps.
 11. The method ofclaim 1, wherein the absorbance of the tube at one half the laserwavelength is at least 2 to 10 times the absorbance of the tube withoutthe absorber.
 12. The method of claim 1, wherein the absorber comprisesa compound including a phenyl ring.
 13. The method of claim 1, whereinthe absorber comprises butylated hydroxytoluene (BHT) or methyl paraben.14. The method of claim 1, wherein the polymer is poly(L-lactide) 15.The method of claim 1, wherein the absorber comprises metallic orinorganic compounds.
 16. A method of laser machining a substrate to forma stent, comprising: providing a tube comprising a poly(L-lactide)(PLLA) and an absorber; and laser machining the polymer tube with alaser beam having a pulse width of 1 to 12 ps and with a laserwavelength of 515 or 532 nm, wherein the absorber has a maximumabsorbance in a range between 200 and 300 nm and an extinctioncoefficient at least 2 times larger than the polymer in the range, andwherein the absorber increases absorption of the laser energy whichallows the laser machining to cut through the wall in one pass of thelaser beam using a laser cutting speed of 4 to 20 in/min to form ascaffold comprising structural elements.
 17. The method of claim 16,wherein the absorber has a content of less than 1 wt % of the tube andprovides an absorbance of the tube at 258 nm that is at least 2 timesthe absorbance of the polymer or tube without the absorber.
 18. Themethod of claim 16, wherein the absorber has a content of less than 0.1wt % of the tube and provides an extinction coefficient weight percentof the tube at 258 nm that is at least 2 times the absorbance of thetube without the absorber.
 19. A method of laser machining a substrateto form a stent, comprising: providing a tube comprising a bioresorbablealiphatic polyester polymer and an absorber; and laser machining thepolymer tube with a laser beam to form a scaffold, wherein the laserbeam has a pulse width that provides multiphoton absorption of laserenergy from the laser beam, wherein the polymer is transparent to laserenergy at a wavelength of the laser beam, and wherein the absorber has aweight percent extinction coefficient at least 100 times greater thanthe polymer at one half the wavelength of the laser beam, and whereinthe absorber increases ablation of the polymer by the laser beam. 20.The method of claim 19, wherein the absorber has a content of less than0.01 wt % of the tube and provides an absorbance of the tube at one halfthe laser wavelength that is at least 2 times the absorbance of thepolymer or tube without the absorber.
 21. The method of claim 19,wherein the absorber has a content of less than 0.1 wt % of the tube andprovides an absorbance of the tube at one half the laser wavelength thatis at least 10 times the absorbance of the polymer or tube without theabsorber.